ECCN Students

By Adugnaw Am.(MSc)
adugnaw3ambelu@gmail.com
 Objectives
At the end of this chapter the student will be able to:
1. Define functional structure of neurons.
2. List the 2 divisions of the nervous tissue.

3. Enumerate functions of neuron & neuroglia.

4. Explain the membrane potential, graded potential and

action potential.

5. Discuss Synapses and synaptic transmission.

Outlines
Overview of the nervous system.
Functional structure of neurons.
Classification of neurons and neuralgia, properties.
The membrane potential, RMP, ion channels.
Action potential (nerve impulse), properties.
Graded potential and action potential, differences.
Propagation (conduction) of nerve impulse.
Synapses and synaptic transmission.
Overview of the nervous system
 Among the 11 body systems, the nervous system & the
endocrine system play the most important roles in
maintaining homeostasis.

 The NS can respond rapidly to help adjust body processes

using nerve impulses.

 The ES typically operates more slowly & exerts its influence

on homeostasis by releasing hormones that the blood
delivers to cells throughout the body.
 Overview of the NS…
The NS is an intricate, highly organized network of
billions of neurons & even more neuroglia.
Human brain has an estimated number of 1011
Neurons and 1014 Synapses.
Principal cell types that make up the nervous
system are:
Neurons &
Neuroglial cells
 Overview of the NS…

Neurons
 Functional, signal conducting cells specialized for:
 Sensory function
 Generation of thought
 Storage of memory
 Integrates idea
 Coordinates muscular activities
 Overview of the NS…
Neuroglia
 Supporting cells.
 20x outnumber neurons.
(the guy to the right had an
inordinate amount of them)
 Can multiply after maturation.
 Potential causes of glioma.
(brain tumour)
Neurons

Functional & structural units of the nervous system.

Specialized to conduct information from one part of
the body to another.
A neuron has 3 distinct parts;
Cell body/Soma, Dendrites, Axon
 Neurons…

There are different types of neurons but most have

certain structural and functional characteristics in
common:
Cell body (soma)
One or more specialized, slender processes
(axons/dendrites)
An input region (dendrites/soma)
A conducting component (axon)
A secretory (output) region (axon terminal)
 Soma

Contains nucleus plus most normal organelles.

Biosynthetic center of the neuron.
Contains a very active & developed rough
endoplasmic reticulum (RER) which is responsible
for the synthesis of neurotransmitters (NTs).
neuronal RER is referred to as the Nissl body.
Contains many bundles of protein filaments
(neurofibrils) which help to maintain the shape,
structure, and integrity of the cell.
 Soma…

Contain multiple mitochondria. Why?

Acts as a receptive service for interaction with other
neurons.
Most somata are found in the bony environs of the
CNS. Why?
Clusters of somata in the:
CNS are known as nuclei
PNS are known as ganglia
Neuronal Processes

Armlike extensions emanating from every neuron.

CNS consists of both somata & processes whereas
the bulk of the PNS consists of processes.
Tracts = Bundles of processes in the CNS
Nerves = Bundles of processes in the PNS
2 types of processes that differ in structure &
function:
Dendrites & Axons
Neuronal Processes…
Dendrites
 Thin, branched processes whose main function is
to
receive incoming signals.
 Effectively increase the surface area of a neuron to
increase its ability to communicate with other
neurons.
 Small, mushroom-shaped dendritic spines further
increase SA
 Convey info towards the soma thru the use of
graded potentials.
Neuronal Processes…
Axons (Myelinated /unmylinated)

 Most neurons have single axon (long up to 1m) process

 Convey info away from the cell body.

Originates from axon hillock.

 Transmit APs from the soma toward the end of the axon where
they cause NT release.

 Often branch sparsely, forming collaterals.

Each collateral may split into telodendria which end in a

synaptic knob, which contains synaptic vesicles-
membranous bags of NTs.
Neuronal Processes…
Axolemma = axon plasma membrane. Surrounded
by a myelin sheath, a wrapping of lipid which:
Protects the axon & electrically isolates it
Increases the rate of AP transmission
This wrapping is never complete. Interspersed along
the axon are gaps where there is no myelin – these
are nodes of Ranvier.
The myelin sheath is made by ________ in the
CNS & by _________in the PNS.
Functional classification of
neurons
 There are three classes of neurons:

1. Sensory (afferent) neurons

- Conduct impulses from periphery to the center

2. Motor (efferent) neurons

-Conduct impulses from CNS to the periphery

3. Interneuron (association neurons)

- Integrative

- Conduct impulses from sensory to motor area.

 Morphological classification of
Neurons
• Structurally neurons are classified into 3 classes:
1. Multipolar neurons
 Found in the CNS
 Motor in function
2. Bipolar neurons:
 Found in retina & inner ear
 Sensory in function
3. Unipolar neurons:
 Located in the ganglia of
spinal & cranial nerves.
 Sensory in function
 The Neuroglia
 Non neural cells found in association with
neurons.
 Provide supporting functions to the nervous
system.
 They are:
1. Microglial cells
2. Astrocytes
3. Oligodendrocytes
4. Ependymal cells
5. Schwann cells
6. Satelite cells
The Neuroglia…
1. Microglial cells
 Specialized immune cells
that act as the macrophages
of the CNS.
 Why is it important for the
CNS to have its own army of
immune cells??????
2. Astrocytes
 Star-shaped, abundant &
versatile(Diversified).
 Provide nourishment to the
CNS & involved in the
formation of the blood brain
barrier (BBB).
The Neuroglia
3.Oligodendrocytes
 Produce myelin sheath
which provides electrical
insulation for certain
neurons in the CNS.
4. Ependymal Cells
 Low columnar epithelial
cells that line ventricles of
the brain & the central
canal of the spinal cord.
 Some are ciliated which
facilitates the mov’t of
cerebrospinal fluid (CSF).
 Neuroglia…cont’d
5. Schwann Cells
• Form myelin sheaths
around larger nerve fibers in
the PNS.
• Vital to neuronal
regeneration.
6. Satellite Cells
• Small cells that line the
exterior surface of PNS.
• Regulate the external
chemical environment.
Neuroglia…cont’d
 Resting Membrane Potential
All cells have a voltage difference across their plasma
membrane = membrane potential (VM) .
 Membrane potential
at rest is called resting
membrane potential (RMP).
 At rest, there are:
 Electro positivity out &
 Electro negativity inside the
cell membrane of the neuron.
What are the causes of the RMP?
1. Outward diffusion of K+ through K+ leak
channels.
 ECF is very high in Na+ while ICF is very high in
K+.
 As a result, K+ is constantly leaking out of cell.
2. Na+/K+ pump is constantly pumping 3Na+ ions out &
2K+ ions in for every ATP used.
 Thus more positive charge is leaving than entering.
3. Protein Anions (Proteinates)
 Negatively charged proteins within the ICF that
cannot travel through the PM.
RMP…cont’d
Selective Permeability of Membranes
 Some ions permitted to cross more easily than
others.
 Neuronal membranes contain ion channels, protein
tubes that span the membrane:
I. Non-gated
 Stay open all the time.
II. Gated
 Open on the occasion of action potential, causing
a change in the permeability of the membrane.
Selective…cont’d
Electrical potentials exist across the membranes of
virtually all cells of the body.
In addition, some cells, such as nerve & muscle
cells,
are capable of generating rapidly changing
electrochemical impulses at their membranes
These impulses are used to transmit signals
along the nerve or muscle membranes.
 Basic Electrophysiological Terms
 Excitability:

ability of the cell to generate the action potential.

 Excitable Cells:

Cells that generate action potential during

excitation.

In excitable cells (muscle, nerve, secretery cells),

the action potential is the marker of excitation.
Basic Electrophysiological
Terms…
 Stimulus:
A sudden change of the internal or external
environmental condition of the cell.

 Threshold (Intensity):
The lowest or minimal intensity of stimulus to elicit
an action potential.
Basic Electrophysiological Terms…
Polarization:
A state in which membrane is polarized at rest,
negative inside & positive outside.

Depolarization:
The membrane potential becomes less negative
than the resting potential (-70 mV).
Basic Electrophysiological Terms…
 Repolarization:
• when the membrane
returns to the resting
potential after
depolarization.
 Hyperpolarization:
• membrane potential
become More Negative
than the resting
potential (-70 mV).
Electrical Potentials
1. Graded Potential (GP)
Local changes in membrane potential.
Serves as short distance signals.
Initiates action potentials if threshold is reached.
Found at receptor site

2. Action potential (AP)

Sends signals over longer distances.
It is all or none phenomena
 Graded Potentials

Produced by a specific triggering mechanism

(stimulus) that causes the opening of gated ion
channels usually Na+ channels,
which opens in response to stimuli causing Na+ to move
into(influx) the cell (depolarization).

Their initial amplitude may be almost any size –

It simply depends on how much Na+ originally entered
cell.
Graded Potentials…
If the initial amplitude of the GP is sufficient, it will
spread all the way to the axon hillock where V-gated
channels reside.
If the arriving potential change is suprathreshold,
AP will be initiated in the axon hillock & will travel down the
axon to the synaptic knob where it will cause NT
exocytosis.

If the potential change is subthreshold,

no AP will ensue & nothing will happen.
 Graded Potentials…
 Graded potentials vary in magnitude (Strength)
Stronger the stimulus →more channels open → more
positive charges enter → more depolarization
Longer the duration of the stimulus → longer the duration
of the graded potential.
Graded Potentials…
• Graded potentials can be depolarizing or
hyperpolarizing.
Graded potentials lose strength with
increasing distance from the site of origin.
 Action Potentials
 Rapid, reversible & conductive change of the
membrane potential.
• Single action potential involves only a small portion
of the total excitable membrane.
• No loss of strength as they travel along the
membrane (nondecremental propagation).
Nerve signals are transmitted by action potentials.
 Action Potentials
 If VM reaches threshold, Na+ channels open & Na+ influx
ensues, depolarizing the cell and causing the VM to increase.
This is the rising phase of an AP
 Eventually, the Na+ channel will have inactivated & the K+
channels will be open. Now, K+ effluxes & repolarization
occurs.
This is the falling phase.
 K+ channels are slow to open & slow to close. This causes
the VM to take a brief dip below resting VM.
 This dip is the undershoot & is an example of
Hyperpolarization.
Action Potentials…cont’d
Once an action potential is initiated at the axon
hillock, no other triggering is necessary.
The original action potential triggers an identical
new action potential in the adjacent area of the
membrane.
Action Potentials…cont’d
Contiguous Conduction
–AP spreads along every patch of the membrane
down the axon.
Refractory Periods…cont’d
Imagine, if you will, a toilet.
 When you pull the handle, water floods the
bowl.
 This event takes a couple of seconds & you
cannot stop it in the middle. Once the bowl
empties, the flush is complete. Now the
upper tank is empty. If you try pulling the
handle at this point, nothing happens
(Absolute Refractory).
 Wait for the upper tank to begin refilling.
You can now flush again, but the intensity
of the flushes increases as the upper tank
refills (Relative Refractory)
 All-or-None Principle
• A threshold or suprathreshold stimulus applied to
a single nerve fiber always initiates action potential
 Threshold depolarization action potential
 Suprathreshold depolarization action potential
• Subthreshold depolarization no action potential
Myelination
Fibbers covered with myelin sheath (mostly lipid) at
regular intervals along an axon.
Once initiated, the speed that AP moves down an
axon depends on axon mylination and diameter.
 Myelinated – fast
 Unmyelinated – slow
 The larger – the faster
Myelin-forming Cells
Both are examples of glial cells
 Oligodendrocytes
Found in the central nervous system (CNS)
One oligodendrocyte - several myelin sheaths on
different axons

 Schwann cells
Peripheral nervous system (PNS)
One Schwann cell - one myelin sheath on one axon
Myelin-forming Cells…cont’d
Peripheral Nervous System Central Nervous System
Myelination in the
CNS
Myelination in the PNS
 Nervous system
 The nervous system is unique

In vast complexity of thought processes & control actions it

can perform.

Each minute it receives literally millions of bits of information

from different sensory nerves & sensory organs and then
integrates all these to determine responses to be made by the
body.
Introduction to Nervous system….
It is one of the two major regulatory systems

90 % - glial cells (supporting),

Serves as the connective tissue of the nervous
system.

CNS receives trillions of input

CNS processes this input,

Initiates appropriate response

Acts by means of its Action Potentials

 Introduction to Nervous system…

Two main divisions

1. Central Nervous System(CNS)
It collects /receives information,
analyze it & synthesize
Make decision what to do
2. Peripheral nervous system (PNS)
has two parts
Motor and Sensory
Organization of the NS
Organization of the Nervous System
 Nervous system…..
-A system that controls all of the activities of the body.
-It is made up of: brain, spinal cord, nerves & senses.

The The spinal cord

brain

The The
nerves senses
Cells of the NS
Neuron
Neuroglia
 Central nervous system

1) Frontal lobe -motor &motor association area

2) Parietal lobe - sensory & sensory association

3) Temporal lobe–auditory & auditory association

4) Occipital lobe –visual & visual association

5) Limbic lobe- olfaction, memory, emotion &

autonomic
Synapse
 Neurotransmitters
They are endogenous chemical substances
Are found in the axon terminal
Released by action potential (by
depolarization of the presynaptic neuron
induced by Ca++ influx)
They will bind to their receptors on the post
synaptic cell
Receptors change shape
Results in
EPSP or IPSP
 CLASSIFICATION OF NEUROTRANSMITTERS
Classe Neurotransmitters Receptors Distribution,
s role
I Acetylcholine (Ach) Nicotinic receptors Excitatory in
Muscarinic receptors CNS, PNS
II Adrenaline, nor-adrenaline α & β adrenoreceptors Excitatory
Amines Dopamine Dopaminergic Rs: A, B Inhibitory in
Histamine Histaminergic Rs: H1 & 2 BG
Excitatory
III GABA (γ-amino butyric GABA-A & B receptors Inhibitory in
Amino acid) Glycine receptors BG
Acids Glycine NMDA receptors Inhibitory
Aspartate NMDA receptors Excitatory
Glutamate Excitatory
IV Hypothalamic Hormones, Hormone receptors Stimulatory or
Polype Pituitary Hormones, Ang-II Inhibitory
p
 Neurotransmission in CNS

The CNS controls the main functions of the body

through the actions of endogenous chemical
substances known as “neurotransmitters”

Drugs that influence behavior and improve the

functional status of patients with neurological or
Psychiatric diseases act by

Enhancing or blunting the effectiveness of one or

a combination of specific transmitters & channels
 Neurotransmitters in CNS
Biogenic amines:
Ach, NA, DA, 5-HT, Histamine
Amino acids:
Excitatory (Glutamate & Asparate)
Inhibitory (GABA & Glycine)
(eg.opioid, somatostatin)
Others: Neuropeptides
Purines (such as adenosine and ATP),
NO and Arachidonic acid derivatives
 GABA

Major inhibitory aa in the mammalian CNS

It occurs only in brain tissues, and is
abundant in the nigrostriatal system
Formed from glutamate by the action of
Glutamic acid decarboxylase (GAD)
Destroyed by a transamination reaction
catalyzed by GABA transaminase
Types of GABA receptors

GABAA

Most prominent GABA-receptor subtype

Ligand gated ion channel receptor

Increase Cl- Conductance (Postsynaptic)

Site of action of many neuroactive drugs

 GABA…

GABA deficiency/defect causes excessive

stimulation

Seizure

Picrotoxin and bicuculline are convulsants

BDZs and barbiturates are anticonvulsants

 GABA…

GABAB

•G protein coupled receptor

• Interacts with Gi to inhibit adenylyl cyclase, activate

K+ channels,& reduce Ca2+ conductance

• Largely Presynaptic, inhibit transmitter release

• Baclofen (agonist ) which used to treat spasticity

and related motor disorders
Glycine
another inhibitory CNS neurotransmitter

Co-agonist at NMDA receptors

Found predominantly in the ventral horn of the spinal

cord

Blockade of Glycine receptors cause seizure

Best known drug is the convulsant agent called

Strychnine (Glycine antagonist)

 Strychnine is a potent spinal cord convulsant & used as a

rat poison
 Glutamate
Major Excitatory Neurotransmitter

Widely distributed in the CNS-75-80% of CNS

synapses

Synthesized within the brain

Excessive stimulation may lead to Seizure

 Glutamate Receptors
are most abundant in the cortex, basal
ganglia and Sensory Pathway

It has multiple Receptors

E.g. NMDA (N-methyl D-aspartate)

 Dopamine (DA)
 NT & a precursor for NA
 Function
Nigrostriatal (substantia nigra to striatum)
Motor control
Deficiency of dopamine in this system causes
“Parkinson’s disease”.
Mesolimbic/mesocortical (ventral tegmental midbrain to
n.accumbens, hippocampus, and cortex)
Increased dopaminergic activity in this system is
believed to cause “schizophrenia”.
 Dopamine contd..

Common brain function disorders related with

DA
Parkinson's disease…..decreased DA

Psychosis/ schizophrenia…..increased DA

Nausea & vomiting-- by stimulating dopamine receptors

D2 receptor mediated

Dopamine (DA) Receptor Distribution
Dopamine Type Site of Receptors
Receptors
D1 Gs Neostratum,cerebral crtex,olfactory
tubercle, nucleus accumbus
D2 Gi neostriatum; olfactory tubercle;
nucleus accumbens
D3 Gi nucleus accumbens; islands of
Calleja
D4 Gi Midbrain; Amygdala;
Hippocampus; Hypothalamus
D5 Gs
Key : Gi= Inhibitory
Gs= Excitatory
 Dopamine Receptors…
 Dopamine receptors play an essential role in daily life
functions.
 This hormone & its receptors affect
 Movement,
 Emotions &
 The reward system in the brain.
Dopamine receptors are expressed in the central nervous
system,
Specifically in the
Hippocampal
Dentate gyrus &
Subventricular zone.
 Dopamine Receptors …
 Dopamine receptors are also expressed in the periphery,
more prominently in
Kidney &
Vasculature
 There are five types of dopamine receptors, which
include
D1, D2, D3, D4, & D5.
Each receptor has a different function.
 Dopamine Receptors …..
 The function of each dopamine receptor

 D1: memory, attention, impulse control, regulation of renal

function, locomotion

 D2: locomotion, attention, sleep, memory, learning

 D3: cognition, impulse control, attention, sleep

 D4: cognition, impulse control, attention, sleep

 D5: decision making, cognition, attention, renin secretion

 Dopamine Receptors….
 Five d/t dopamine receptors can subdivide into two categories.

 D1 & D5 receptors group together, &

 D2, D3, D4 are together in a separate subgrouping.

 D1 & D5 receptors couple to G stimulatory sites & activate

adenylyl cyclase.

 Activation of adenylyl cyclase leads to production of the 2nd

messenger cAMP, which leads to the production of protein
kinase A (PKA) w/h leads to further transcription in the
nucleus
 Dopamine Receptors….
D2 through D4 receptors couple to G inhibitory sites, w/h
inhibit adenylyl cyclase & activate K+ channels.

D1 receptor is the most abundant out of the five in the central
nervous system, followed by D2, then D3, D5 & least abundant is
D4 .

D1 receptors help regulate the dev’t of neurons when

dopamine hormone binds to it.
Dopamine Receptors….
D1 & D5 receptors, along with stimulating adenyl
cyclase, also activate phospholipase C, which
leads to the induction of intracellular calcium
release & activation of protein kinase C.

Protein kinase C is a calcium-dependent protein

kinase.
 Dopamine Receptors ….
 Calcium is also involved in modulating neurotransmitter
release by exocytosis.
D1 & D5 receptors are also involved in the kidney by
inhibiting Na/K ATPase through PKA and PKC pathways.
In the kidneys, these receptors correlate with an increase
in electrolyte excretion and renal vasodilation
 D2, D3, and D4 receptors are expressed mainly in the
 Striatum
External globus pallidus
Core of nucleus accumbens
Hippocampus
Amygdala &
Cerebral cortex.
Dopamine Receptors….

 These receptors also affect the postsynaptic receptor-

medicated extrapyramidal activity.

 D2-D4 receptors are important in the signaling for the

survival of human dopamine neurons & neuronal
development
 Dopamine cont’d..

 Common brain function disorders related with DA

Parkinson's disease…..decreased DA

Psychosis/ schizophrenia…..increased DA

Nausea & vomiting-- by stimulating dopamine receptors

D2 receptor mediated

 Dopamine cont’d..

 Common brain function disorders related with DA

Parkinson's disease…..decreased DA

Psychosis/ schizophrenia…..increased DA

Nausea & vomiting-- by stimulating dopamine receptors

D2 receptor mediated

 Norepinephrine
 The only small NT synthesized inside synaptic Vesicles at
Synaptic Terminal instead of in cytoplasm of the terminal

 Synthesized from β hydroxylation of dopamine

 The most prominent cluster of NA-neurons is the locus

ceruleus (LC)

 The LC also projects to the spinal cord and is involved in the

descending control of pain

 Other NA- ergic neurons lie close to LC in the pons &

medulla
 NE functions
 Arousal and mood
LC neurons are silent during sleep, and their
activity increases with behavioural arousal
its reduction will contribute to occurrence of
depression
Imipramine and amitriptyline (NE reuptake
inhibitors)
 Serotonin ( 5-HT)
Most of the serotonin in the brain is in the
brainstem, specifically in the raphe nuclei
Can exert inhibitory or excitatory effects on
individual neuron acting either pre or post-
synaptically
Synthesized from tryptophan, an amino acid
derived from dietary protein
 Serotonin ( 5-HT)

Following release, 5-HT is largely recovered by

neuronal uptake

Selective serotonin reuptake inhibitors constitute

an important group of antidepressant drugs

5-HT is degraded almost entirely by monoamine

oxidase
Serotonine ( 5-HT) Receptors
 Main receptor subtypes in CNS: 5-HT1A, 5-HT1B, 5-HT1D ,5-
HT2 and 5-HT3

 All are G-protein-coupled receptors except for 5-HT3, which

is a ligand-gated cation channel

 5-HT1 receptors are predominantly inhibitory in their

effects

5-HT1A receptors are expressed as autoreceptors by the

5-HT neurons in the raphe nuclei

limit the firing of cells in raphe & limbic system

the main target of drugs used to treat anxiety &

5-HT1B and 5-HT1D receptors are found mainly as
presynaptic inhibitory receptors in the basal ganglia.
Agonists acting on peripheral 5-HT1D receptors
are used to treat migraine(eg. Sumatriptan)
5-HT2 receptors exert an excitatory postsynaptic
effect, and are abundant in the cortex and limbic
system.
Many antipsychotic drugs are antagonists at 5-
HT2A receptors
5-HT3 receptors are found chiefly in
the area postrema
involved in vomiting
are excitatory ionotropic receptors
specific antagonists (e.g.
Ondansetron) are used to treat
nausea and vomiting caused by
chemotherapy
5HT4-R (in striatum)
has presynaptic effect to increase
ACh release
5-HT Functions
Involved
feeding behaviour
5-HT2 receptor antagonists (
antipsychotics) increase appetite and
cause weight gain.
antidepressant drugs that inhibit 5-HT
uptake (serotonin reuptake inhibitors)
cause loss of appetite
Acetylcholine

Widely distributed in CNS

Ach receptors
Both nicotinic and muscarinic (predominantly
M1) ACh receptors occur in the CNS
Muscarinic receptors appear to mediate
the main behavioural effects associated with ACh, namely effects
on arousal, on learning, short-term memory and
movement coordination
Muscarinic antagonists (e.g. scopolamine)
cause amnesia when used as preanaesthetic
medication
Abnormalities of cholinergic pathways

Parkinsonism- relatively excessive Ach

function
Muscarinic Ach antagonist(Benzotropine)
Alzheimer - profound cholinergic
neuron loss in the hippocampus
associated with memory loss
cholinesterase inhibitor(Revastigmine)
 Histamine
present in the brain in much smaller amounts
than in other tissues
Neurons originate in
Magnocellular nuclei in posterior hypothalamus
(called tuberomamillary nucleus)
Histamine acts on three types of receptor (H1-
3)
all of which are G-protein-coupled receptors
H1 and H3 receptors are mainly excitatory; H2
receptors are inhibitory
H1 receptor antagonists are antiemetic &
strongly sedative
 Somatic Sensory System: Introduction
Sensory receptors – general
Are specialized epithlial cell or neurons that
Monitor specific conditions in the body or external
environment
Transduce environmental signals into neural signals
Each receptor has a characteristic sensitivity
Environmental signals that can be detected include :
Mechanical force
Light
Sound
Chemicals and
Temperature
Sensory information is processed by the thalamus
and transmitted to the cerebral cortex
Attributes of a stimulus that are mediated by
sensory system:
• Modality (quality)
• Intensity (amount)
• Duration
• Location
Modality (quality)
Five major types of qualities:
Vision, hearing, touch, taste and smell
information is represented in a series of APs
by process called neural encoding
Intensity (amount) - by frequency
Attributes of a stimulus that are
mediated by sensory system…
Modality of sensations – labelled line code (Law of
specific nerve energies)
Each of the principal types of sensation that we can
experience pain, touch, sight, sound, etc. – is called
a modality of sensation
How is it that different nerve fibers transmit
different modalities of sensation?
There are two major ways / reasons:
 Differential sensitivities of receptors
 Because that each nerve tract terminates at a specific
point in the CNS
This specificity of nerve fibers for transmitting only one
modality of sensation is called the law of specific
nerve
energies or “labeled line” principle.
Order of neurons that transit
information to the Cerebral Cortex
• First-order neurons
Are the primary afferent neurons that receive the
transduced signal and send the information to the
CNS
Cell bodies of the primary afferent neurons are in the
dorsal root or spinal cord ganglia
• Second-order neurons
Are found in the spinal cord or brain stem
Receive information from one or more primary
afferent neurons in relay nuclei and transmit it to the
thalamus
Axons of the second-order neurons usually cross
the midline in a relay nucleus in the spinal cord
before they ascend to the thalamus
(Therefore, sensory information originating on one
Order of neurons that transit
information to the Cerebral Cortex…
Third-order neurons
Are located in the relay nuclei of the
thalamus.
From there, encoded sensory information
ascends to the cerebral cortex
Fourth-order neurons
 Are located in the appropriate sensory area
of the cerebral cortex.
The information received results in a
conscious perception of the stimulus
 Receptor Potential
 All sensory receptors have feature in common
 It first causes a local potential called a receptor
potential
The receptor potential in turn excites action potentials
in the nerve fiber
Steps in Sensory transduction
Stimulus arrives at the sensory receptor
Ion channels are opened in the sensory receptor
 Usually currents are inward – produces
depolarization
 The exception in photoreceptor, where light
causes
hyperpolarization
• The changes inn membrane potential produced by
the stimulus is the receptor potential, or
generator
Different receptors can be excited in
several different ways to cause receptor
potential:
 Mechanical deformation
Application of chemical
Changing the temperature
By electromagnetic radiation
Somatic Sensory System: Receptor Potential,….
 TYPES OF SENSORY RECEPTORS
There are basically two types of sensory receptors
Somatic senses
Special senses
• Electromagnetic receptors
• Chemoreceptors
which detect taste in the mouth, smell in the
nose
O2 and CO2 level in the arterial blood
Osmolarity of the body fluids
SOMATIC SENSES SENSORY
RECEPTORS
1. Mechanoreceptors
2. Thermoreceptors
3. Nociceptors
 1. Mechanoreceptors
These receptors respond to five tactile
qualities: • Pressure

• Touch

• Vibration (Kinesthetic sense)

• Tickle (tactile senses)

• Position senses
 2. Thermo receptors

The free nerve ending are involved as receptors

These are three types of thermoreceptors;
A. The cold receptors
Most areas of the body have 3 to 10 times as many
cold spots as warmth spots
transmitted by small type Aδ myelinated nerve ending
at velocities of about 20 m/sec.
B. The warm receptors
 transmitted mainly over type C nerve fibers at
velocities of only 0.4 to 2 m/sec.
C. Pain receptors (freezing cold or burning hot)
stimulated only by extreme degrees of heat or cold
Fig. Discharge frequencies at different skin temperatures of a cold-pain fiber,
a cold fiber, a warmth fiber, and a heat-pain
fiber.
Types of Sensory Receptors….
3. Nociceptors/ Pain Receptors
Pain receptors are free nerve endings
They are widespread in the superficial layers
of various organs
• Different stimuli exert pain receptors
 Mechanosensitive pain receptors
 Thermosensitive pain receptors
 Chemosensitive pain receptors
 Neurophysiology of Pain
Pain occurs whenever
Nociceptors (Latin nocere, •to hurt'").
Tissues are being damaged & causes the
individual to react to remove the pain
stimulus.
Possible Causes
Tissue damage
Ischemia
Muscle Spasm
Causes of pain
Tissue damage as a cause of pain
During tissue damage, chemicals can cause direct damage
of nerve fibers
Production of chemicals as a result of damage (bradykinin
& some of the PG) cause extreme stimulation of nerve
fibers
The release of the chemicals not only:
Stimulates the Chemosensitive pain receptors but
also greatly decrease the threshold for stimulation of
the mechanosensitive & thermosensitive pain
receptors as well
E.g. Extreme pain caused by slight mechanical or heat
stimuli following tissue damage as seen in a burn
 Causes of Pain--
Ischemia
Tissue ischemia causes pain
Accumulation of lactic acid due to the anaerobic
metabolism
 Formation of Bradykinin, Proteolytic Enzymes
because of cell damage
Muscle Spasm
This is very common,
Direct effect of muscle spasm in stimulating
Mechanosensitive pain receptors
Indirect effect through spasm causing ischemia
 Qualities of Pain
The sense of pain (nociception) can be
subdivided into a number of qualities with
respect to both:
 Character of the Pain
Fast pain
Slow pain
Site of Origin
Somatic Pain &
Visceral Pain
Pain Modality
PAIN

Somatic Visceral

Superficial Deep
pain pain

Initial Delayed
Pain pain

Connective tissue, Visceral

Skin
bones, joints muscles

Gall
Gall &
+ Kidney
Kidney
Pinprick Muscle cramp Stones, Ulcers
Pinching Headache appendicitis
Types of pain and their qualities
Two major types of pain :
Fast pain
Felt within about 0.1 second after a pain stimulus is
applied
Sharp pain, pricking pain, acute pain, and electric
Slow pain.
Pain begins only after 1 second or more and then
increases slowly over many seconds and sometimes
even minutes.
Has many names, such as
Slow burning pain, aching pain, throbbing pain, nauseous
pain, and chronic pain
Usually associated with tissue destruction
Can occur both in the skin and in almost any deep
Pain receptors and their stimulation
The pain receptors in the skin and other
tissues are all free nerve endings.
They are widespread
In the superficial layers of the skin, as
well as
In certain internal tissues, such as the
Periosteum, the arterial walls, the
joint surfaces, and the falx and
tentorium in the cranial vault.
Most other deep tissues are only sparsely
supplied with pain endings.
Pain receptors and their stimulation...
 Three Types of Stimuli Excite Pain Receptors;
Mechanical
Thermal, &
Chemical.
 In general, fast pain is elicited by the
Mechanical &
Thermal types of stimuli, whereas
 Slow pain can be elicited by all three types.
The chemical substances are especially important in
stimulating it
Pain receptors and their stimulation...

 Some of the chemicals that excite the chemical type of pain

are

Bradykinin, serotonin, histamine, potassium ions, acids,

acetylcholine, and Proteolytic enzymes.

In addition, Prostaglandins & Substance P enhance

the sensitivity of pain endings but do not directly excite

them.

 In contrast to most other sensory receptors of the body,

pain receptors adapt very little & sometimes not at all.
Transmission Of Pain Signals Into The
Central Nervous System
The two pathways(Dual Pathways ) mainly
correspond to the two types of pain
A fast-sharp pain pathway &
A slow-chronic pain pathway.
PERIPHERAL PAIN FIBERS—“FAST” &
“SLOW” FIBERS
 The fast-sharp pain signals
are elicited by either mechanical or thermal pain
stimuli.
 They are transmitted in the peripheral nerves to the
spinal cord by small type Aδ fibers at velocities
between 6 & 30 m/sec.
 Conversely, the slow-chronic type of pain
 is elicited mostly by chemical types of pain stimuli but
sometimes by persisting mechanical or thermal
stimuli.
This slow-chronic pain is transmitted to the spinal cord
by type C fibers at velocities between 0.5 & 2 m/sec.
 Peripheral dual pain Pathways…
 Upon entering the spinal cord from
the dorsal spinal roots, the pain
fibers terminate on relay neurons in
the dorsal horns.

 Here again, there are two systems

for processing the pain signals on
their way to the brain as indicated
in the fig below
Dual pain pathways in
the spinal cord and brain stem
 Upon entering the spinal cord, the pain signals take two
pathways to the brain, through

The Neospinothalamic tract &

The Paleospinothalamic tract.

 Neospinothalamic Tract

 It is for Fast Pain.

 The fast type Aδ pain fibers transmit mainly mechanical &

acute thermal pain.

 They terminate mainly in lamina I (lamina Marginalis) of the

dorsal horns, as shown in the fig above
Neospinothalamic Tract…

They excite second-order neurons of the

Neospinothalamic tract.

These second-order neurons give rise to long fibers

that cross immediately to the opposite side of the
cord through the anterior commissure and then turn
upward, passing to the brain in the anterolateral
columns.

Neospinothalamic Tract termination in the Brain

Stem & Thalamus
Fig. Transmission of pain signals
into the brain stem, thalamus, and
cerebral cortex by way of the fast
pricking pain pathway
and the slow burning pain pathway.

 Nervous System has the

Capability to Localize Fast
Pain in the Body.
Paleospinothalamic Pathway
It is important for Transmitting Slow Chronic Pain.

The Paleospinothalamic pathway is a much older

system and
transmits pain mainly from the peripheral slow-chronic
type C pain fibers, although it does transmit some
signals from type Aδ fibers as well.
 Paleospinothalamic Pathway
 In this pathway, the peripheral fibers terminate in the spinal
cord almost entirely in laminae II & III of the dorsal horns,
which together are called the Substantia Gelatinosa.

 Substance P, the probable slow-chronic neurotransmitter of

type C nerve endings
 Slow chronic Pathway….
 The nervous system has poor capability to localize precisely
the source of pain transmitted in the slow chronic pathway.

 This phenomenon is in keeping with the multisynaptic,

diffuse connectivity of this pathway.

 It explains why patients often have serious difficulty in

localizing the source of some chronic types of pain.
Mechanism of Referred Pain
 Often a person feels pain in a part of the body that is fairly
remote from the tissue causing the pain.

This phenomenon is called referred pain.

 When the visceral pain fibers are stimulated, pain signals

from the viscera are conducted through at least some of the
same neurons that conduct pain signals from the skin, and
the person has the feeling that the sensations originate in the
skin.
Fig. Mechanism of referred pain and referred hyperalgesia. Neurons 1 & 2
receive pain signals from the skin as well as from the viscera.
 VISCERAL PAIN
 Pain from the different viscera of the abdomen & chest.

 Often, the viscera have sensory receptors for no other

modalities of sensation besides pain.

 Also, visceral pain differs from surface pain in several

important aspects.

Highly localized types of damage to the viscera seldom

cause severe pain
 Causes of True Visceral Pain
Any stimulus that excites pain nerve endings in diffuse
areas of the viscera can cause visceral pain.

Such stimuli include;

Ischemia of visceral tissue,

Chemical damage to the surfaces of the viscera,

Spasm of the smooth muscle of a hollow viscus,

 Causes of True Visceral Pain….

Excess distention of a hollow viscus, and

Stretching of the connective tissue surrounding or within

the viscus.

 Essentially all visceral pain that originates in the thoracic

and abdominal cavities is transmitted through small type C
pain fibers &,

Therefore, can transmit only the chronic-aching-

suffering type of pain.
 PAIN SUPPRESSION
(ANALGESIA) SYSTEM
IN THE
BRAIN AND SPINAL CORD
Neurotransmitters involved in Analgesia
(Pain Inhibition)
 Several transmitter substances are involved in the analgesia
system; especially involved are

Enkephalin & Serotonin.

 Many nerve fibers derived from the

Periventricular Nuclei and from the

Periaqueductal Gray Area

Secrete enkephalin at their endings

(in the raphe magnus nucleus ).

Neurotransmitters involved in Analgesia…
 Fibers originating from the raphe magnus nucleus

Send signals to the dorsal horns of the spinal cord to

secrete serotonin at their endings.

 The serotonin causes

local cord neurons to secrete enkephalin as well.

 The Enkephalin is believed to cause

Both Presynaptic & Postsynaptic Inhibition of incoming

type C and type Aδ pain fibers where they synapse in the
dorsal horns
Fig. Analgesia system of the
brain and spinal cord,
showing
(1) inhibition of incoming pain
signals at the cord level &
2) presence of enkephalin-
secreting neurons that
suppress pain signals in
both the cord & the brain stem.
 CNS
BRAIN AND SPINALCORD
 Spinal cord
Extends from foramen magnum – 2nd lumbar
vertebra
Has central grey H-shaped portion & peripheral
white portion.
Close to spinal cord, sensory and motor nerve fibers
separate into dorsal & ventral root.
Spinal nerves are 31 pairs:
 8 … Cervical
 12 … Thoracic
 5 … Lumbar
 5 … Sacral
 1 … Coccygeal (coccyx)
 Spinal Cord…
The spinal cord has Two Functions:

1. Common passageway for ascending & descending

tracts.
- Neurons in the white matter of the spinal cord transmit :

◊ Sensory signals from peripheral regions to the brain &

motor signals from the brain to peripheral regions.

2. Centre For Reflexes.

- Neurons in the gray matter of the spinal cord:

◊ Integrate incoming sensory information & respond with motor

impulses that control muscles or glands.
 Gray matter & white matter
 Microscopically, the CNS contains 2 neural elements:
Neuron cell bodies (clusters are known as nuclei)
Nerve fibers/axons (in bundles called tracts)

 Macroscopically, CNS tissues distinguished by color:

 Gray matter
Consists of Somata, dendrites & unmyelinated axons.
 White matter
Consists primarily of myelinated axons.
 Spinal Cord Tracts
 Spinal cord white matter contains:

 Ascending tracts

Transmit sensory information from receptor to higher

level of CNS

 Descending tracts

Originate from different cortical areas & brain stem

nuclei.

 Transmit motor information from higher center to the

effector structures
 Spinal Cord Tracts …
Ascending Tracts Descending Tracts
Carry information related to: Carry information
Touch, pain, temperature, associated with
2 point discrimination, motor activity like:
position & vibration Posture
Example Balance
◊ Lateral Spinothalamic tracts Muscle tone
- Pain, temperature & crude touch Somatic reflex
◊ Dorsal column tracts Visceral reflex
- Position & vibration
 Reflex
 Fast & involuntary response to a stimulus that doesn’t
involve conscious thought.
 Most reflexes involve spinal cord / brain stem & do not
involve higher brain centers.
Reflex action
 Consists of an action that is signalled to CNS & a
reaction sent by the CNS.
Reflex Arc
 Nerve pathway that is responsible for triggering reflex
action.
 Simplest pathway capable of receiving a stimulus &
yielding a response.
 Basic functional unit of nervous system.
Basic Components of the Reflex Arc
1.Receptor
- detects changes and generates action potential (AP).
2. Afferent (sensory) pathway
- conducts AP to CNS.
3. Integrating centre
- Interprets & coordinate the changes.
 spinal cord, brain stem, hypothalamus ,cerebral
cortex.
4. Efferent (motor) pathway
- conducts AP to effectors
5. Effector
- receive feed back and respond accordingly.
Components of the reflex arc…
 BRAIN
Brain regions
1. Cerebrum
2. Diencephalon
 Thalamus
 Hypothalamus
3. Brainstem
 Midbrain
 Pons
 Medulla
oblongata
Cerebellum
4. Cerebellum
 Cerebrum
 Largest portion of the brain (80% by mass).

 Responsible for higher mental functions concerning:

Perception of fine sensation

Learning, memory, speech

Judgment

Planning

 Corpus callosum:

Major tract of axons that functionally interconnects right

& left cerebral hemispheres.
 Cerebral Cortex
3 types of functional areas:
1. Motor
- control voluntary motor
functions.
M
2. Sensory S
A
- allow for conscious
recognition of stimuli.
3. Association
- integration.
Cerebral cortex …
Cerebral cortex
…
Each hemisphere contains 4 lobes:
frontal, parietal, occipital & temporal.
Has an outer cortex of gray matter
surrounding an interior that is mostly white
matter, except for a few small portions.
The surface is marked by ridges called
gyrus separated by grooves called sulcus.
Each gyrus contains one or more
functional areas called Brodmann´s areas.
Cerebral cortex …
Brodmann´s areas of cerebral cortex
 Functions of lobes of the brain
1. Frontal Lobe = conscious thought; damage can result in
mood changes, social differences, etc. It is the most
uniquely human of all the brain structures.
2. Parietal Lobe = plays important roles in integrating
sensory information from various senses, and in the
manipulation of objects; portions of the parietal lobe are
involved with Visuospatial processing.
3. Occipital Lobe = sense of sight; lesions can produce
hallucinations.
4. Temporal Lobe = senses of smell and sound, as well as
processing of complex stimuli.
Brodmann´s Areas of Cerebral
Cortex …
Sensory Areas

 Found in the parietal, occipital & temporal lobes.

1. Somatosensory cortex.
2. Somatosensory association cortex.
3. Visual areas.
4. Auditory areas.
5. Olfactory cortex.
6. Gustatory cortex.
7. Vestibular cortex.
Sensory
Areas …
Language Areas
 Wernicke’s area
 understanding oral
& written words.
 Broca’s area
 speech production.

 Lateral prefrontal
cortex
 language
comprehension &
complex word
analysis
Other brain parts

Thalamus
Hypothalamus
Basal nuclei
The Brain Stem
Sleep
It is physiological state of temporary
cessation of consciousness.
It is defined as unconsciousness from
which a person can be aroused by
sensory stimuli.
 Sleep ...
 Physiological changes during sleep
 CVS: ↓Vasomotor tone, ↓ABP, ↓CO
 Respiratory system: ↓PVR, ↓TV
 Muscles relaxed.
 Mechanism of sleep
- Inhibition of RAS by 2 centres in the brain stem.
a. The medullary raphe magnus which releases
serotonin as a NT inhibits the RAS to induce sleep.
b. The pontin nucleus which depressed the RAS.
Cerebellum
Lies inferior to the
cerebrum & occupies
the posterior cranial
fossa.
2nd largest region of the
brain:
 10% of the brain by
volume, but
contains 50% of
neurons.
Cerebellum…
 Coordinates rapid, automatic adjustments, that
maintain balance & equilibrium.
 Control of muscle tone
 Control of voluntary movement
The Limbic system
Forebrain nuclei & fiber
tracts that form a ring
around the brain stem.
Center for basic
emotional drives.
Consists of structures
that make the border
between neocortex &
BS.
Has 2 components
 Function of the limbic system
1. Olfaction:
 Oldest function of the limbic system. It is concerned with
perception, discrimination & coordination of olfactory
sensation.
2. Emotion:
 Amygdala & HT control the somatic, autonomic, endocrine
& behavioral responses in state of emotion.
 Stimulation of amygdaloid nuclei produces anger, fear or
rage.
 Destruction of amygdaloid nuclei abolishes fear and
aggression.
Function of the limbic system
(cont´d)
3. Memory:
 It plays an important role in sorting out the information &
deciding which info to be stored in memory as well as for
encoding & consolidation of memory.
 LS, particularly, hippocampus & amygdala play crucial
role in memory & learning.
4. Motivation:
 It contains the reward & punishment centers which are
responsible for motivation to take or avoid certain
actions.
 Function of the limbic system
(cont´d)
5. Control of feeding behavior:
 LS, particularly the amygdala is concerned with
sorting out the type of food into edible & inedible
type.
 Lesion to amygdaloid nuclei results in
hyperphagia.
 The subject with amygdaloid lesion tries to eat any
available unlike lesion to the hypothalamic satiety
center.
6. Control of the ANS.